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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 66 - 66
22 Nov 2024
RADIOIMMUNOTHERAPY COMBATING METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS AND ITS BIOFILM IN VITRO
Ye Z van der Wildt B Vogely C Weinans H Poot A van der Wal B
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Aim

Prosthetic joint infections (PJI) remain a great challenge in orthopedic surgery with a high mortality rate. It is particularly complicated by biofilms and infections caused by Methicillin-resistant Staphylococcus aureus (MRSA). It concurrently shields bacteria from host immune responses and confers resistance to antibiotics. This study aims to investigate the efficacy of radioimmunotherapy as an innovative therapeutic modality to address the challenges posed by MRSA and its biofilm.

Method

We induced specific monoclonal antibodies 4497-IgG1 as carriers, which target wall teichoic acids (WTA) existing on MRSA and its biofilm. Radionuclides actiniumr-225 (225Ac, α-emitter) and lutetium-177 (177Lu, β-emitter) were conjugated with mAbs using DOTA as chelator. Quality control was assessed using thin layer chromatography and immunoreactivity assays. 225Ac- and 177Lu-labelled 4497-IgG1 were employed to evaluate the susceptibility of MRSA and its biofilm to the radioimmunotherapy in vitro. Planktonic MRSA and biofilms, at concentrations of 108 and 107 CFU/mL, were incubated at 37°C for 60 minutes in PBS containing either 225Ac-mAb (0 - 14.8 kBq) or 177Lu-mAb (0 - 14.8 MBq). Radiolabelled dunituximab and free radionuclides serve as isotype-matched negative control. The bacterial viability and metabolic activity were subsequently quantified using CFU and XTT assays.

Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 31 - 31
1 Oct 2022
BIODISTRIBUTION OF A RADIO-LABELLED ANTIBODY TARGETING STAPHYLOCOCCUS AUREUS IMPLANT INFECTION IN MICE
v. Dijk B v. Duyvenbode FH de Vor L Nurmohamed FRHA Lam M Poot A Ramakers R Koustoulidou S Beekman F v. Strijp J Rooijakkers S Dadachova E Vogely HC Weinans H van der Wal BC
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Aim

Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. Herewith we introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide the biodistribution and specificity in a mouse implant infection model.

Methods

4497-IgG1targeting S. aureus Wall Teichoic Acid was labeled to Indium-111 using “CHXA” as a chelator. SPECT-CT scans were performed at 24, 72 and 120 hours after administration in Balb/cAnNCrl mice with a subcutaneous implant pre-colonized with biofilm of S. aureus. Biodistribution over the various organs of this labelled antibody was visualized and quantified using SPECT-CT imaging and compared to uptake at the target tissue with implant infection.

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